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Intranasal oxytocin for social psychopathology: mechanisms of action and predictive biomarkers using neuroimaging, genetics and artificial intelligence.

Mental illness is by far the largest contributor to chronic illness in Europe, entailing half of all social welfare expenditure (WHO, 2008). However, neuropsychiatry lags behind other fields of medicine, both in the understanding of disease mechanisms and in the prediction of treatment response. This severely limits symptom recovery and people?s quality of life. With the present proposal, focused on the neuropeptide oxytocin (OT) and its promising pharmacological use, we aim to improve both the pathophysiological and the therapeutic models of SCZ, with a focus on (the much neglected) social cognitive symptomatology. We also promote an alternative to the black-box, and one-size-fits-all clinical tradition. We will answer 2 questions:
1) What is the impact of intranasal oxytocin (OT) on the SCZ patient?s social cognition neurocorrelates – and how is this influenced by dopamine(DA)-ergic pharmacotherapies and relevant genetic variability?
2) Can we predict in advance how much will a SCZ patient?s striatal function respond to intranasal OT, by applying artificial intelligence (AI) to genetic, DAergic medication and neuroimaging data collected previous to administration? This interdisciplinary project, unique in Portugal, is a double-blind and randomised-controlled pharmacological manipulation of OT (with naturalistic DAergic medication), and a pharmacogenetic assessment of DA and OT genetic influence, on brain function during a social game (the Prisoner?s Dilemma) which elicits social reward and trust processing. Apart from a hypothesis-driven approach to characterize the OT and DA pathway overlap, we also employ a hypothesis-free AI approach towards a predictive biomarker for OT ? of translational, cost-efficient potential.
This endeavour stems from: 1) the PI?s current pioneering work at iMM where she, as an award-winning Marie Curie Fellow, started characterizing the OT and DA interplay on social cognition in healthy subjects; 2) her previous work on the etiology, DA antagonists treatment response and onset prediction biomarkers of SCZ combining genetics and neuroimaging, at the Institute of Psychiatry (King?s College London, KCL), and 3) the co-PI?s development of novel neuroimaging tools and AI models to serve as biomarkers, and 4) the recent creation of NeuroPsyCAD, founded a result of their highly complementary lines of work.
Team-wise, this project offers a triangulation between: 1) a peer-to-peer academic collaboration between an applied and a technical academic biomedical institution of (iMM and IBEB, respectively) 1) a novel academic-clinical collaboration with Psychiatric wards in 3 Lisbon hospitals, and 3) an academic-industrial joint-venture with a newly founded company NeurPsyCAD; notwithstanding international collaborations with KCL and Emory University (US) ? in sum, an extremely valuable opportunity for students and researchers in Portugal to train in, and advance cutting interdisciplinary neuroscience and psychiatry.